Anne Griffiths

University of Toronto, Toronto, Ontario, Canada

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Publications (129)800.68 Total impact

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    ABSTRACT: Oral methotrexate (MTX) administration avoids weekly injections, reduces costs and may improve quality of life of patients with Crohn's disease (CD), especially children. Routes of administration have never been systematically compared in CD. We aimed to compare effectiveness and safety of orally (PO) versus subcutaneously (SC) administered MTX in paediatric CD. 226 children with CD treated with oral or subcutaneous MTX were included in a multicentre, retrospective 1-year cohort study (62% boys, mean age 13.8±2.8 years, 88% previous thiopurines). 38 (17%) were initially commenced on oral, 98 (43%) started subcutaneous and switched to oral and 90 (40%) were treated with subcutaneous only. Matching and 'doubly robust' weighted regression models were based on the propensity score method, controlling for confounding-by-indication bias. 11/23 pretreatment variables were different between the groups, but the propensity score modelling successfully balanced the treatment groups. 76 children (34%) had sustained steroid-free remission with a difference that did not reach significance between the PO and the SC groups (weighted OR=1.72 (95% CI 0.5 to 5.9); p=0.52). There were no differences in need for treatment escalation (p=0.24), elevated liver enzymes (p=0.59) or nausea (p=0.85). Height velocity was lower in the PO group (p=0.006) and time to remission was delayed in the PO group (p=0.036; Fleming (0, 1) test). In this largest paediatric CD cohort to date, SC administered MTX was superior to PO, but only in some of the outcomes and with a modest effect size. Therefore, it may be reasonable to consider switching children in complete remission treated with subcutaneous MTX to the oral route with close monitoring of inflammatory markers and growth. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.
    Gut 11/2014; DOI:10.1136/gutjnl-2014-307964 · 13.32 Impact Factor
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    ABSTRACT: Background In the treatment of Crohn's disease (CD), mucosal healing has become a major goal, with the hope of avoiding intestinal damage from chronic inflammation. Magnetic resonance enterography (MRE) has emerged as a non-invasive means of monitoring inflammation and damage.AimsAs part of the development of MRE-based multi-item measures of inflammation and damage for paediatric studies, we carried out a systematic review and meta-analysis to identify MRE variables used to describe these two distinct concepts.Methods2501 studies of MRI and CD were identified. Studies written in any language reporting individual MRE signs for patients diagnosed with CD were included. Two-hundred-and-forty-four studies were fully reviewed and 62 were included (inflammation, n = 51; damage, n = 24). Sensitivity, specificity and associated confidence intervals were calculated, and hierarchical summary ROC curves were constructed for each MRE sign.ResultsA total of 22 MRE signs were used to reflect inflammation, and 9 to reflect damage. Diagnostic accuracy of MRE signs of inflammation and damage was heterogeneous; however, wall enhancement, mucosal lesions and wall T2 hyperintensity were the most consistently useful for inflammation (most sensitivities >80% and specificities >90%), and detection of abscess and fistula were most consistently useful for damage (most sensitivities >90%, specificities >95%).Conclusions Identifying the best MRE variables to reflect inflammation and damage will maximise the utility of this rapidly emerging technique and is the first stage of constructing MRE-based indices for evaluating inflammation and intestinal damage.
    Alimentary Pharmacology & Therapeutics 11/2014; DOI:10.1111/apt.13024 · 4.55 Impact Factor
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    ABSTRACT: Methotrexate (MTX) is an immunomodulator used in pediatric inflammatory bowel disease (IBD) maintenance regimens. However, MTX use is associated with liver toxicity. We aimed to systematically review and meta-analyze the incidence of hepatotoxicity with MTX use among children with IBD. We searched MEDLINE, EMBASE, Web of Science, and Cochrane Central Register of Controlled Trials databases from 1946 to April 2013 for cohort studies and collected information about the study design, IBD treatment results, and hepatotoxicity. Pooled proportions of toxicity with 95% confidence interval (CI) were estimated using a random-effects model. Twelve high-quality studies were included in this review. Fifty-seven of 457 patients treated with MTX developed varied degrees of abnormal liver biochemistry. The pooled proportion of patients with abnormal liver biochemistry was 10.2% (95% CI 5.4%-18.5%) across all studies included in the meta-analysis. Due to hepatotoxicity, dose reductions were required in 6.4% (95% CI 4.3%-9.5%), whereas 4.5% (95% CI 2.8%-7.2%) of patients required discontinuation. Hepatotoxicity after the use of MTX among IBD patients was a relatively common event. Monitoring for hepatotoxicity is strongly recommended, as discontinuation of MTX may be necessary in a significant proportion of children.
    Inflammatory Bowel Diseases 11/2013; DOI:10.1097/01.MIB.0000436953.88522.3e · 5.48 Impact Factor
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    ABSTRACT: To assess infliximab pharmacokinetics in pediatric ulcerative colitis (UC). This phase 3, randomized, open-label multicenter study enrolled 60 children (6-17 yr) with moderate-to-severely active UC (Mayo score, 6-12; endoscopic subscore, ≥2), despite conventional therapy. Patients received infliximab 5-mg/kg induction infusions at weeks 0, 2, and 6. Week 8 clinical responders (n = 45) were randomized to infliximab 5 mg/kg given every (q) 8 weeks through week 46 or every 12 weeks (q12w) through week 42. Patients losing response during maintenance infliximab were eligible to increase the dose (5→10 mg/kg) and/or shorten the dosing interval (q12w→q8w). Blood samples were collected for infliximab concentration and pharmacokinetic determinations. Infliximab pharmacokinetics was not influenced by age (6-11 yr versus 12-17 yr), baseline immunomodulator use, or the extent of UC. At week 8, higher serum infliximab concentrations (≥41.1 μg/mL) were associated with greater proportions of patients achieving efficacy endpoints (clinical response, 92.9%; mucosal healing, 92.9%; and clinical remission, 64.3%) versus those with lower serum concentrations (<18.1 μg/mL; 53.9%, 53.9%, and 30.8%, respectively). At week 30, higher median trough serum infliximab concentrations were observed with infliximab 5 mg/kg q8w (1.9 μg/mL) versus q12w (0.8 μg/mL) and with infliximab 10 mg/kg (2.9 μg/mL) versus 5 mg/kg (1.1 μg/mL) among patients who are regimen adjusted. Infliximab pharmacokinetics/exposure-response relationship in patients with UC aged 6 to 17 years were generally comparable with those observed in reference adult UC populations, supporting using infliximab 5 mg/kg at weeks 0, 2, and 6 followed by maintenance dosing with 5 mg/kg q8w in these patients. A positive relationship was noted between serum infliximab level and clinical effect following induction therapy similar to adults.
    Inflammatory Bowel Diseases 11/2013; 19(13). DOI:10.1097/01.MIB.0000435438.84365.f7 · 5.48 Impact Factor
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    ABSTRACT: OBJECTIVES:: Despite a paucity of published supporting data, 5-aminosalicylate (5-ASA) use in pediatric ulcerative colitis (UC) is common. This study describes the use and outcome of a large multicenter inception cohort of children with UC treated with 5-ASA. METHODS:: Data were obtained from the Pediatric Inflammatory Bowel Disease Collaborative Research Group Registry, a prospective North American observational study of newly diagnosed children with IBD≤16 years of age. Patient data are recorded at diagnosis, 30 days, and then quarterly. Patients are managed by physician dictate not protocol. Disease activity is classified by physician global assessment (PGA). The primary outcome examined was corticosteroid (CS)-free, inactive UC at 1 year following initiation of 5-ASA within 30 days of diagnosis (with or without concomitant CS use) without the need for rescue therapy (immunomodulators, biologics or colectomy). RESULTS:: Study subjects included 213 patients newly diagnosed with UC who received oral 5-ASA compounds (115 of whom also received CS) during the first 30 days after diagnosis, and no other oral therapies for the treatment of UC. Of these 213 patients, 86 (40%) were CS-free and PGA inactive at 1 year without rescue. Outcome was not associated with disease severity at diagnosis, demographic or laboratory factors examined, or initial dose of 5-ASA used. CONCLUSION:: 40% of children started on 5-ASA as primary maintenance therapy at diagnosis are in corticosteroid free remission after 1 year of treatment. Further pediatric studies will be needed to address whether increased adherence and/or higher dosing schedules will improve outcomes.
    Journal of pediatric gastroenterology and nutrition 07/2012; 56(1). DOI:10.1097/MPG.0b013e31826ac41a · 2.87 Impact Factor
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    ABSTRACT: The IMAgINE 1 study (NCT00409682) evaluated the safety and efficacy of adalimumab double-blind maintenance dosing regimens following open-label induction for pediatric patients with moderate to severe Crohn's disease (CD). We studied 192 patients with Pediatric Crohn's Disease Activity Index (PCDAI) scores >30 for whom conventional treatment was unsuccessful. Patients received open-label induction therapy with subcutaneous adalimumab at weeks 0 and 2 (160 mg and 80 mg, or 80 mg and 40 mg, for body weight ≥40 kg or <40 kg). At week 4, 188 patients were assigned to groups based on achievement of clinical response (defined as decrease in PCDAI ≥15 points from baseline; 155/188 [82.4%]) and prior exposure to infliximab (82/188 [43.6%]). Groups were given double-blind maintenance therapy with adalimumab at high (40 mg or 20 mg for body weight ≥40 kg or <40 kg; n = 93) or low doses (20 mg or 10 mg for body weight ≥40 kg or <40 kg; n = 95) every other week for 48 weeks. Clinical remission (PCDAI ≤10) at week 26 (the primary end point) was compared between groups using the Cochran-Mantel-Haenszel test, adjusting for strata, with nonresponder imputation. Adverse events were monitored to evaluate safety. A total of 152 of 188 patients (80.9%) completed all 26 weeks of the study. At week 26, 63 patients (33.5%) were in clinical remission, with no significant difference between high- and low-dose groups (36/93 [38.7%] vs 27/95 [28.4%]; P = .075). No new safety signals were detected. Adalimumab induced and maintained clinical remission of children with CD, with a safety profile comparable to that of adult patients with CD. More children who received high compared with low dose were in remission at week 26, but the difference between dose groups was not statistically significant.
    Gastroenterology 05/2012; 143(2):365-74.e2. DOI:10.1053/j.gastro.2012.04.046 · 13.93 Impact Factor
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    ABSTRACT: Budesonide (BUD) is being used in pediatric Crohn disease (CD) because it is believed to have the potential to reduce corticosteroid-related toxicity; however, few data are available describing its use. The aim of the present study was to describe BUD use in an inception cohort of pediatric patients with CD. Data were derived from the prospective Pediatric IBD Collaborative Research Group Registry established in 2002 in North America. Use of BUD in children with CD was examined. BUD was used in 119 of 932 (13%) of children with newly diagnosed CD, with 56 of 119 (47%) starting BUD ≤ 30 days of diagnosis (26/56 with ileum and/or ascending colon [IAC] disease). BUD was used as monotherapy (9%), in combination with 5-aminosalicylates (77%), or in combination with immunomodulators (43%). Forty-three percent (24/56) went on to receive conventional corticosteroid at some point following their first BUD course. For the 63 of 119 (53%) who started BUD beyond the diagnosis period, 51 of 63 (81%) also received prednisone, with BUD used as a means of weaning from prednisone in 17 of 63 (27%). Patients with IAC disease who received BUD ≤ 30 days of diagnosis were just as likely to have received conventional corticosteroids by 1 year as were those who did not receive BUD ≤ 30 days of diagnosis. Two-thirds (77/119) of patients received BUD for ≤ 6 months. BUD is being used among pediatric patients newly diagnosed as having CD, although the majority does not have disease limited to the IAC. BUD monotherapy was rare, and further data are required to better define the role of BUD in the treatment of pediatric CD.
    Journal of pediatric gastroenterology and nutrition 01/2012; 55(2):200-4. DOI:10.1097/MPG.0b013e31824a09c2 · 2.87 Impact Factor
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    The Journal of pediatrics 01/2012; 160(3):530-1. DOI:10.1016/j.jpeds.2011.11.048 · 3.74 Impact Factor
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    ABSTRACT: We evaluated the efficacy and safety of infliximab for inducing and maintaining benefit in children with moderately to severely active ulcerative colitis (UC). Patients (6-17 years old) who had active UC (Mayo scores of 6-12; endoscopic subscores ≥ 2) and had not responded to or tolerated conventional treatment were given 5 mg/kg infliximab at weeks 0, 2, and 6. The primary end point was response at week 8 (decreases in Mayo scores ≥ 30% and ≥ 3 points and decreases in rectal bleeding subscores of ≥ 1 or an absolute subscore of ≤ 1). At week 8, only responders were randomly assigned to groups given infliximab every 8 or 12 weeks (q8w or q12w) and followed through week 54. Maintenance end points included pediatric UC activity index scores <10 points, defined as remission. At week 8, infliximab induced a response in 73.3% of patients (44 of 60) (95% confidence interval, 62.1%-84.5%; a positive result was defined by 95% confidence interval lower limit >40%). Among responders, twice as many were in remission at week 54 after q8w (8 of 21, 38.1%) than q12w (4 of 22, 18.2%; P = .146) therapy. Assuming the q8w remission rate for responders, the overall remission rate at week 54 would be 28.6%. Serious adverse events and infusion reactions occurred in similar proportions in the q8w and q12w groups. No deaths, malignancies, opportunistic infections, tuberculosis, or delayed hypersensitivity reactions were reported. Infliximab was safe and effective, inducing a response at week 8 in 73.3% of pediatric patients with moderate to severely active UC who did not respond to conventional therapy. The overall remission rate at week 54 for all enrolled patients was 28.6%, assuming the more effective q8w remission rate.
    Clinical gastroenterology and hepatology: the official clinical practice journal of the American Gastroenterological Association 12/2011; 10(4):391-9.e1. DOI:10.1016/j.cgh.2011.11.026 · 6.53 Impact Factor
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    ABSTRACT: Assess long-term effects of maintenance infliximab therapy in children with moderately-to-severely active Crohn's disease. One hundred twelve patients with a Pediatric Crohn's Disease Activity Index (PCDAI) score >30 received infliximab 5 mg/kg at weeks 0, 2, and 6 in the REACH study. Patients considered responders at week 10 were randomized to infliximab 5 mg/kg every 8 (q8w) or 12 (q12w) weeks. Patients who completed treatment through week 46, and who the investigator believed would benefit from continued treatment, could enter the open-label extension (OLE) and receive up to three additional years of infliximab. No hypothesis testing was performed. www.clinicaltrials.gov, identifier: NCT0020767. Sixty children entered the OLE: 33, 12, and 15 patients were receiving infliximab 5 mg/kg q8w, 5 mg/kg q12w, and 10 mg/kg q8w, respectively, at extension entry. Patients receiving infliximab for up to 3 years during the OLE maintained clinical benefit, with approximately 80% of patients consistently having no to mild disease activity per the physician's global assessment and very good to fair health in the past 2 weeks per the patient and parent/guardian global assessments. Patients with ≥1-year delay in bone age at baseline trended toward improvement in height during the OLE. Respiratory system disorders, most commonly upper respiratory infections, were the most prevalent adverse events reported; six (10%) patients had serious infections. Among children with moderately-to-severely active Crohn's disease who received infliximab for 46 weeks in REACH and then for up to 3 additional years in the REACH OLE, infliximab was effective in maintaining clinical benefit and was generally well-tolerated.
    Current Medical Research and Opinion 03/2011; 27(3):651-62. DOI:10.1185/03007995.2010.547575 · 2.37 Impact Factor
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    ABSTRACT: Despite little supporting data, thiopurine use is common in pediatric ulcerative colitis (UC). Our aim was to determine outcome following thiopurine use in a multicenter inception cohort of children diagnosed with UC. Data were obtained from a prospective observational study of newly diagnosed children <16 years of age. Data are recorded at diagnosis, 30 days, and quarterly. Patients are managed by physician dictates not protocol. Disease activity is classified by physician global assessment. The primary outcome was corticosteroid (CS)-free inactive UC at 1 year following thiopurine initiation without the need for rescue therapy (infliximab, calcineurin inhibitors, or colectomy). Of 1,490 patients in our registry, 394 have UC (mean age at diagnosis 11.3±3.7 years); 197 (50%) received thiopurine (49% ≤3 months from diagnosis). Also, 84% were receiving CSs and 60% 5-aminosalicylates at thiopurine start. Of the 197 patients, there was insufficient follow-up (41), previous or concomitant use of infliximab (16), or calcineurin inhibitor (7), leaving 133 patients evaluable at 1 year. Of these, 65 (49%) had CS-free inactive UC without rescue therapy. CS-free inactive disease at 1 year after initiating thiopurine was not affected by starting thiopurine ≤3 months vs. >3 months from diagnosis, gender, age, or concomitant treatment with 5-aminosalicylates. Kaplan-Meier analysis showed that the likelihood of remaining free of rescue therapy in the thiopurine-treated patients was 73% at 1 year. Approximately 50% of children with UC starting thiopurine without previous or concomitant biologic or calcineurin inhibitor therapy have CS-free inactive disease 1 year later without the need for rescue therapy.
    The American Journal of Gastroenterology 01/2011; 106(5):981-7. DOI:10.1038/ajg.2010.493 · 9.21 Impact Factor
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    ABSTRACT: Crohn's disease and ulcerative colitis are complex disorders with some shared and many unique predisposing genes. Accurate phenotype classification is essential in determining the utility of genotype-phenotype correlation. The Montreal Classification of IBD has several weaknesses with respect to classification of children. The dynamic features of pediatric disease phenotype (change in disease location and behavior over time, growth failure) are not sufficiently captured by the current Montreal Classification. Focusing on facilitating research in pediatric inflammatory bowel disease (IBD), and creating uniform standards for defining IBD phenotypes, an international group of pediatric IBD experts met in Paris, France to develop evidence-based consensus recommendations for a pediatric modification of the Montreal criteria. Important modifications developed include classifying age at diagnosis as A1a (0 to <10 years), A1b (10 to <17 years), A2 (17 to 40 years), and A3 (>40 years), distinguishing disease above the distal ileum as L4a (proximal to ligament of Treitz) and L4b (ligament of Treitz to above distal ileum), allowing both stenosing and penetrating disease to be classified in the same patient (B2B3), denoting the presence of growth failure in the patient at any time as G(1) versus G(0) (never growth failure), adding E4 to denote extent of ulcerative colitis that is proximal to the hepatic flexure, and denoting ever severe ulcerative colitis during disease course by S1. These modifications are termed the Paris Classification. By adhering to the Montreal framework, we have not jeopardized or altered the ability to use this classification for adult onset disease or by adult gastroenterologists.
    Inflammatory Bowel Diseases 01/2011; 17(6):1314-21. DOI:10.1002/ibd.21493 · 5.48 Impact Factor
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    ABSTRACT: Genome-wide association studies and candidate gene studies in ulcerative colitis have identified 18 susceptibility loci. We conducted a meta-analysis of six ulcerative colitis genome-wide association study datasets, comprising 6,687 cases and 19,718 controls, and followed up the top association signals in 9,628 cases and 12,917 controls. We identified 29 additional risk loci (P < 5 x 10(-8)), increasing the number of ulcerative colitis-associated loci to 47. After annotating associated regions using GRAIL, expression quantitative trait loci data and correlations with non-synonymous SNPs, we identified many candidate genes that provide potentially important insights into disease pathogenesis, including IL1R2, IL8RA-IL8RB, IL7R, IL12B, DAP, PRDM1, JAK2, IRF5, GNA12 and LSP1. The total number of confirmed inflammatory bowel disease risk loci is now 99, including a minimum of 28 shared association signals between Crohn's disease and ulcerative colitis.
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    Nature Genetics 01/2011; · 29.65 Impact Factor
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    ABSTRACT: To compare four faecal markers for their ability to predict steroid refractoriness in severe paediatric ulcerative colitis (UC). Construct validity and responsiveness to change were also assessed. This was a prospective multicentre cohort study. Stool samples from 101 children (13.3 + or - 3.6 years; Pediatric UC Activity Index (PUCAI) at admission 72 + or - 12 points) were obtained at the third day of intravenous steroid therapy. Repeated samples at discharge were obtained from 24 children. Predictive validity was assessed using diagnostic utility statistics to predict steroid failure (ie, the need for salvage treatment). Concurrent validity was assessed using correlational analysis with the following constructs: PUCAI, Lindgren and Seo scores, physician's global assessment, albumin, erythrocyte sedimentation rate and C-reactive protein (CRP). Responsiveness was assessed using test utility and correlational strategies. Median values (IQR) were very high at baseline for all four markers (calprotectin 4215 microg/g (2297-8808); lactoferrin 212 microg/g (114-328); M2-pyruvate kinase (M2-PK) 363 U/g (119-3104); and S100A12 469 microg/g (193-1112)). M2-PK was numerically superior to the other three markers and CRP in predicting response to corticosteroid treatment (area under the receiver operating characteristic (ROC) curve 0.75 (95% CI 0.64 to 0.85; p<0.001) vs <0.65 for the others). However, it did not add to the predictive ability of the PUCAI (area under the ROC 0.81 (95% CI 0.73 to 0.89)). M2-PK also had the highest construct validity but with a modest mean correlation with all constructs (r=0.3; p<0.05). None of the markers was responsive to change (Spearman's rho correlation with change in the PUCAI <0.1; p>0.05, area under the ROC curve <0.65; p>0.05). The four markers were greatly elevated in severe paediatric UC. Only M2-PK had good construct and predictive validity, and none was responsive to change. The PUCAI, a simple clinical index, performed better than the faecal markers in predicting outcome following a course of intravenous corticosteroids in severe UC.
    Gut 09/2010; 59(9):1207-12. DOI:10.1136/gut.2010.211755 · 13.32 Impact Factor
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    ABSTRACT: Infliximab is effective in treating moderate/severe ulcerative colitis (UC) in adults. The aim of this study was to determine the outcome after treatment with infliximab in pediatric UC. We performed a multicenter cohort study of 332 pediatric patients with UC enrolled in the Pediatric Inflammatory Bowel Disease Collaborative Research Group Registry. Children<or=16 years of age and newly diagnosed with UC are enrolled in the registry. Disease and medication information are collected prospectively from the treating physician at diagnosis, 30 days, and quarterly thereafter. No interventions were specified, per protocol. Of 332 patients, 52 (16%) received infliximab (23%<3 months from diagnosis, 38% 3-12 months, 38% >12 months). Mean age at infliximab initiation was 13.3+/-2.6 (range 6-17) years; 87% of patients had pancolitis. Median follow-up was 30 months. Continuous maintenance (CM) therapy was given in 65%, episodic in 21%, episodic converted to CM in 6%, and insufficient data in 8% of patients. Sixty-three percent of patients were corticosteroid refractory, and 35% were corticosteroid dependent. Concomitant medications at first infliximab infusion included corticosteroids (87%), thiopurines (63%), and 5-aminosalicylates (51%). Corticosteroid-free inactive disease by physician global assessment was noted in 12/44 (27%), 15/39 (38%), and 6/28 (21%) patients at 6, 12, and 24 months, respectively. Kaplan-Meier analysis showed that the likelihood of remaining colectomy free after treatment with infliximab was 75% at 6 months, 72% at 12 months, and 61% at 2 years. In this cohort of children with UC receiving infliximab, corticosteroid-free inactive disease was observed in 38 and 21% of patients at 12 and 24 months, respectively. By 24 months, 61% of patients had avoided colectomy.
    The American Journal of Gastroenterology 06/2010; 105(6):1430-6. DOI:10.1038/ajg.2009.759 · 9.21 Impact Factor
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    ABSTRACT: Inflammatory bowel disease, including Crohn's disease (CD) and ulcerative colitis (UC), and type 1 diabetes (T1D) are autoimmune diseases that may share common susceptibility pathways. We examined known susceptibility loci for these diseases in a cohort of 1689 CD cases, 777 UC cases, 989 T1D cases and 6197 shared control subjects of European ancestry, who were genotyped by the Illumina HumanHap550 SNP arrays. We identified multiple previously unreported or unconfirmed disease associations, including known CD loci (ICOSLG and TNFSF15) and T1D loci (TNFAIP3) that confer UC risk, known UC loci (HERC2 and IL26) that confer T1D risk and known UC loci (IL10 and CCNY) that confer CD risk. Additionally, we show that T1D risk alleles residing at the PTPN22, IL27, IL18RAP and IL10 loci protect against CD. Furthermore, the strongest risk alleles for T1D within the major histocompatibility complex (MHC) confer strong protection against CD and UC; however, given the multi-allelic nature of the MHC haplotypes, sequencing of the MHC locus will be required to interpret this observation. These results extend our current knowledge on genetic variants that predispose to autoimmunity, and suggest that many loci involved in autoimmunity may be under a balancing selection due to antagonistic pleiotropic effect. Our analysis implies that variants with opposite effects on different diseases may facilitate the maintenance of common susceptibility alleles in human populations, making autoimmune diseases especially amenable to genetic dissection by genome-wide association studies.
    Human Molecular Genetics 02/2010; 19(10):2059-67. DOI:10.1093/hmg/ddq078 · 6.68 Impact Factor
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    ABSTRACT: Comparison of bowel preparation for colonoscopy in children with either Pico-Salax (sodium picosulphate with magnesium citrate) or polyethylene glycol with electrolyte solution (PEG-ELS). In this investigator-blinded, randomized controlled trial, 83 children (12.5 +/- 3.1 years) requiring elective colonoscopy at a referral hospital were randomly allocated to Pico-Salax (n = 43) or PEG-ELS (n = 40), and an intention-to treat analysis was applied. Pico-Salax was administered in two doses, one the evening before and one on the morning of the procedure. PEG-ELS was administered over 4 hours. Efficacy was scored using the Ottawa scale and other constructs. Tolerability and toxicity were measured by patient and nursing questionnaires and serum biochemistry. 35 of Pico-Salax patients (81 %) were satisfied or very satisfied with the cleanout, compared with 19 (48 %) in the PEG-ELS group (P = 0.001). No differences were found in bowel cleanout effectiveness, as judged by the Ottawa score (P = 0.24), completion rates (P = 0.69), colonoscopy duration (P = 0.59), need for enemas (P = 0.25), or physician's global impression (P = 0.7). Except for one case of mild dehydration in the Pico-Salax group, no clinically significant adverse events were recorded. Serum biochemistry results were similar between groups except for more hypermagnesemia associated with Pico-Salax and hypokalemia with PEG-ELS; neither was clinically significant. Children tolerate Pico-Salax better than PEG-ELS for bowel cleanout before colonoscopy. This study did not demonstrate superiority of effectiveness or safety for either regimen.
    Endoscopy 12/2009; 41(12):1038-45. DOI:10.1055/s-0029-1215333 · 5.20 Impact Factor
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    ABSTRACT: The inflammatory bowel diseases (IBD) Crohn's disease and ulcerative colitis are common causes of morbidity in children and young adults in the western world. Here we report the results of a genome-wide association study in early-onset IBD involving 3,426 affected individuals and 11,963 genetically matched controls recruited through international collaborations in Europe and North America, thereby extending the results from a previous study of 1,011 individuals with early-onset IBD. We have identified five new regions associated with early-onset IBD susceptibility, including 16p11 near the cytokine gene IL27 (rs8049439, P = 2.41 x 10(-9)), 22q12 (rs2412973, P = 1.55 x 10(-9)), 10q22 (rs1250550, P = 5.63 x 10(-9)), 2q37 (rs4676410, P = 3.64 x 10(-8)) and 19q13.11 (rs10500264, P = 4.26 x 10(-10)). Our scan also detected associations at 23 of 32 loci previously implicated in adult-onset Crohn's disease and at 8 of 17 loci implicated in adult-onset ulcerative colitis, highlighting the close pathogenetic relationship between early- and adult-onset IBD.
    Nature Genetics 11/2009; 41(12):1335-40. DOI:10.1038/ng.489 · 29.65 Impact Factor
  • Journal of Crohn s and Colitis Supplements 09/2009; 3(1):2-2. DOI:10.1016/S1873-9954(09)70006-0

Publication Stats

7k Citations
800.68 Total Impact Points

Institutions

  • 1993–2014
    • University of Toronto
      • • Hospital for Sick Children
      • • Department of Paediatrics
      • • Division of Neonatology
      Toronto, Ontario, Canada
  • 1993–2013
    • SickKids
      • Division of Gastroenterology, Hepatology and Nutrition
      Toronto, Ontario, Canada
  • 2009
    • Royal Alexandra Hospital
      Edmonton, Alberta, Canada
    • Riley Hospital for Children
      Indianapolis, Indiana, United States
  • 2007–2009
    • The Children's Hospital of Philadelphia
      • Center for Applied Genomics
      Philadelphia, PA, United States
  • 2008
    • Royal Free London NHS Foundation Trust
      Londinium, England, United Kingdom
  • 2005
    • Duke University
      Durham, North Carolina, United States